In the fields of obstetrics and gynecology, diseases have an effect on pregnancy for various reasons. There is the potential for the onset of an obstetric disease even after having become pregnant, and this may lead to a course of pregnancy that deviates from normal. Due to the effect of more women getting married at a later age attributable to the growing advance of women in society in recent years, there is considerable concern over an increase in the number of late-in-life pregnancies that are susceptible to complication by various obstetric diseases. On the other hand, since pregnancy rates are decreasing with the rise in the age at which women become pregnant, the problem of infertility is also occurring. Although the causes of infertility are categorized into those attributable to men and those attributable to women, those factors attributable to women are further categorized into such factors as ovulation factors, Fallopian tube factors, uterocervical factors or immunological factors. Although assisted reproductive technology (ART) is prominently used to treat this infertility and tremendous progress is being achieved, on the other hand, there is currently little progress being made with respect to other infertility treatment.
Infertility due to uterine factors is said to be caused by changes in the uterine cavity and endometrium. A disease known to be associated with adhesion or degeneration of the uterine cavity is intrauterine adhesion (Asherman's syndrome or IUA) caused by such factors as intrauterine curettage following miscarriage, uterine endoscopic surgery or uterine retained. Although the current method used to treat this intrauterine adhesion consists of surgically synechiotomy or preventing re-adhesion by administration of a hormone preparation following surgery or using an intrauterine device (IUD), there is the problem of frequent recurrence of adhesion. At present, there is no definitive treatment method for such diseases.
IUA causes infertility and menstrual disorders including amenorrhea. Although a study of whether or not patients thought to have IUA can become pregnant without receiving treatment confirmed that 46% of the patients became pregnant, only 30% of the pregnant women achieve term delivery, and placenta accreta was occurred in 13% of the cases (Non-Patent Document 1). Other reports have indicated that placenta accreta occurs in 5% to 31% of such cases. In this manner, IUA has an effect on obstetric complications during pregnancy in addition to infertility and menstrual disorders. Since there are cases in which curettage surgery, which is a cause of endometrial disorders, is unavoidable with respect to postpartum retained placenta and miscarriage surgery, adhesion is considered to occur with a certain probability. Standard treatment for this disease consists of surgical synechiotomy.
Uterine endoscopic surgery is the standard procedure for surgical synechiotomy. Following this surgery, treatment is performed in which a ovarian hormone preparation (such as estrogen) is administered for the purpose of thickening the endometrium. Although it is said that ovarian hormone stimulate the endometrium resulting in re-epithelialization of wound tissue, there is no definitive evidence of this. In addition, there are patients that are unresponsive even after using estrogen and an article was reported the hormone effect is temporary. Since impairment of the basement membrane of the endometrium or fibrosis of the myometrium occurs if estrogen therapy is not successful, there is also the possibility of the occurrence of circulatory and other disorders.
On the other hand, there is support for the use of intrauterine devices (IUD) following surgery, and in contrast to the adhesion rate being roughly 10% in the case of having used an IUD, adhesion has been reported to occur at roughly 50% in the case of not using an IUD (Non-Patent Document 2). In addition, pregnancy rate among 405 infertile patients that used an IUD was 56%, and 123 (60%) of these cases were reported to be normal pregnancies while 42 cases (27%) ended in miscarriage (Non-Patent Document 1). Although the use of an IUD demonstrates a therapeutic effect, it also contains risks. Since an IUD is ultimately a foreign object, there is the possibility of it not being compatible with tissue as well as having the risk of infection. In addition, there is still the potential for re-adhesion even if an IUD is used.
Remarkable progress has been made in the field of regenerative medicine in recent years, and methods are being sought to regenerate various organs. Research is being conducted on the production of organs that retain a three-dimensional structure by using a bioabsorbable polymer as a scaffold and disseminating cells therein. Although biocompatible scaffolds offer the advantages of facilitating handling and the construction of a three-dimensional structure as a result of being a gel, on the other hand, one of the problems is that animal-derived polymers such as collagen or gelatin contain animal components.
In order to solve such problems, culture methods have recently been developed that use culture dishes coated with a temperature-responsive polymer (Patent Documents 1 to 3). According to this technology, cells are able to be transplanted in the form of a tissue sheet. Cardiac output has previously been confirmed to improve in a canine dilated cardiomyopathy model by transplanting a myoblast sheet (Non-Patent Document 3), and studies are being conducted with the aim of practical application to humans. Although a surgical complication of esophageal mucosal resection in the form of stricture of the excised site becomes a problem in the field of esophageal procedures, this stricture has been demonstrated to be able to be prevented by transplantation of a cell sheet that uses autologous oral mucosa epithelial cells (OMEC) to the excised site (Non-Patent Document 4). In the field of ophthalmology, vision has been demonstrated to be restored following damage to corneal epithelium requiring corneal transplant by transplantation of an autologous oral mucosa epithelial cell sheet (OMECs) (Non-Patent Document 5).
Regenerative medicine research is also being conducted in the fields of obstetrics and gynecology. Examples of this research include research for promoting regeneration of uterine tissue by injecting collagen supplemented with vascular endothelial growth factor (VEGF) (Non-Patent Document 6), research for regenerating uterine tissue using collagen as a scaffold (Non-Patent Document 7), and research for formation of cervical-like tissue using a scaffold made of a silk sponge (Non-Patent Document 8).